Details of the Drug Combination

General Information of Drug Combination (ID: DCDAYAJ)

• Drug Combination Name: Chlorhexidine + Amoxicillin
• Indication: Medication Related Osteonecrosis of the Jaw; Status: Phase 4 [1]
• Component Drugs:
  Chlorhexidine (DMQ9MVG): Small molecular drug
  Amoxicillin (DMUYNEI): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Chlorhexidine

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[2]
Gingivitis	DA0B	Approved	[3]
Intracerebral hemorrhage	N.A.	Approved	[3]

Chlorhexidine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Dihydropteroate synthetase (Bact folP)	TT4ILYC	DHPS_ECOLI	Breaker	[6]

Chlorhexidine Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[7]

Indication(s) of Amoxicillin

Disease Entry	ICD 11	Status	REF
Acute otitis media	AB00	Approved	[4]
Bacterial infection	1A00-1C4Z	Approved	[5]
Staphylococcus aureus infection	N.A.	Approved	[4]
Streptococcal pneumonia	N.A.	Approved	[4]
Urinary tract infection	GC08	Approved	[4]
Pneumonia due to Klebsiella pneumoniae	CA40.03	Investigative	[4]
Sinusitis	CA0A.Z	Investigative	[4]

Amoxicillin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Cell membrane (Bact CM)	TTXT4D5	NOUNIPROTAC	Modulator	[8]

Amoxicillin Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[10]
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[10]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[11]

Amoxicillin Interacts with 46 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[12]
Beta-lactamase (blaB)	DED0TBR	A0A414M273_9BACE	Metabolism	[13]
Beta-lactamase (blaB)	DEX8KJO	A6NX15_9FIRM	Metabolism	[14]
Beta-lactamase (blaB)	DEAYSTX	C0W968_9FIRM	Metabolism	[15]
Beta-lactamase (blaB)	DERGEVU	C3WC84_FUSMR	Metabolism	[16]
Beta-lactamase (blaB)	DEV0KWQ	Q8KT52_9BACT	Metabolism	[17]
Beta-lactamase (blaB)	DEQMISO	F9Z530_ODOSD	Metabolism	[16]
Beta-lactamase (blaB)	DEHFJ4G	Q8KT51_9BACT	Metabolism	[16]
Beta-lactamase (blaB)	DEHPJRC	Q8KT60_9BACT	Metabolism	[16]
Beta-lactamase (blaB)	DEITMS0	Q9XBM2_ACIFE	Metabolism	[18]
N-acylhomoserine lactone acylase (lacA)	DEIU0XN	A0A0A1VBK6_9BURK	Metabolism	[19]
Beta-lactamase (blaB)	DET9I1W	BLAC_BACUN	Metabolism	[20]
Beta-lactamase (blaB)	DE7IH52	AMPC_CITFR	Metabolism	[17]
Beta-lactamase (blaB)	DENJ2SQ	BLAB_BACFG	Metabolism	[20]
Beta-lactamase (blaB)	DE5HV8P	A0A4Q5I6I2_9BACE	Metabolism	[20]
Beta-lactamase (blaB)	DE47ARF	B5WXV2_9BACT	Metabolism	[21]
Beta-lactamase (blaB)	DEG2PK9	B5WXV3_BACOV	Metabolism	[20]
Beta-lactamase (blaB)	DEWHJ7A	B5WXV7_BACT4	Metabolism	[20]
Beta-lactamase (blaB)	DEU1RXB	BLAC_BACVU	Metabolism	[20]
Beta-lactamase (blaB)	DETDS7E	A0A2S0LB67_9FLAO	Metabolism	[17]
Beta-lactamase (blaB)	DE37FJH	C6JIU1_FUSVA	Metabolism	[16]
Beta-lactamase (blaB)	DEC7JEF	A0A1S1G219_9NEIS	Metabolism	[17]
Beta-lactamase (blaB)	DEP7MN1	Q9X4S7_PREIN	Metabolism	[22]
Beta-lactamase (blaB)	DEAILCM	A0A246EJV2_9BACT	Metabolism	[22]
Beta-lactamase (blaB)	DET4XFN	Q8KT59_9BACT	Metabolism	[17]
Metallo-beta-lactamase (blaM)	DEPCQ12	Q68K11_ALCXX	Metabolism	[23]
Beta-lactamase (blaB)	DEACNTL	Q2F4C6_SHISO	Metabolism	[24]
Beta-lactamase (blaB)	DEE8742	O32372_CAPOC	Metabolism	[25]
Beta-lactamase (blaB)	DEY09SU	C9MN73_9BACT	Metabolism	[17]
Beta-lactamase (blaB)	DEQLVCA	C9LD75_9BACT	Metabolism	[22]
Beta-lactamase (blaB)	DE2IL34	C2M7J0_CAPGI	Metabolism	[25]
Beta-lactamase (blaB)	DE1NJIW	B6VMJ3_PHOAA	Metabolism	[26]
Beta-lactamase (blaB)	DEDIMN9	A0A413GBG0_9BACE	Metabolism	[20]
Beta-lactamase (blaB)	DEJ8X2W	A0A412YFL9_9BACE	Metabolism	[20]
Beta-lactamase (blaB)	DEFEVNH	A0A381DV31_9FLAO	Metabolism	[25]
Beta-lactamase (blaB)	DEAPGXV	A0A347B2J2_9BACT	Metabolism	[17]
Beta-lactamase (blaB)	DE0PDVC	A0A2A3N1K0_CAPSP	Metabolism	[25]
Beta-lactamase (blaB)	DEQL32N	A0A250F962_9FLAO	Metabolism	[25]
Beta-lactamase (blaB)	DE9HF0I	A0A120A1C6_BACSE	Metabolism	[20]
Beta-lactamase (blaB)	DESHI6O	A0A108T9G3_9BACE	Metabolism	[20]
Beta-lactamase (blaB)	DEZS3N4	A0A069QS91_PRELO	Metabolism	[17]
Beta-lactamase (blaB)	DE5NSUX	A0A095XPV0_9FIRM	Metabolism	[17]
New delhi metallo-beta-lactamase NDM-1 (blaNDM)	DEBGCYQ	A0A345N7K5_SALET	Metabolism	[27]
Beta-lactamase (blaB)	DEW193R	BLA1_KLEPN	Metabolism	[23]
Metallo-beta-lactamase (blaM)	DEK9VG2	BLAN1_KLEPN	Metabolism	[23]
Beta-lactamase (blaB)	DEQ1CTE	A0A2T4TNV5_9BACT	Metabolism	[28]

Amoxicillin Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Affects Expression	[29]
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Affects Expression	[29]
C-C chemokine receptor type 9 (CCR9)	OT5FSOD8	CCR9_HUMAN	Increases ADR	[30]
C-C chemokine receptor type 4 (CCR4)	OT68KZ9B	CCR4_HUMAN	Increases ADR	[30]
HLA class I histocompatibility antigen, A alpha chain (HLA-A)	OTAH14LU	HLAA_HUMAN	Increases ADR	[31]
C-X-C chemokine receptor type 3 (CXCR3)	OTIGS220	CXCR3_HUMAN	Increases ADR	[30]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Increases Expression	[32]
Cytochrome P450 11B2, mitochondrial (CYP11B2)	OTIOLWYN	C11B2_HUMAN	Increases Expression	[32]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Activity	[33]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Increases Expression	[34]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[34]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[34]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Decreases Expression	[35]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[35]
Organic solute transporter subunit alpha (SLC51A)	OTDJRZ0P	OSTA_HUMAN	Increases Expression	[36]

References

• [1] ClinicalTrials.gov (NCT04512638) Best Treatment Choice for Osteonecrosis of the Jaw
• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019822.
• [3] Chlorhexidine FDA Label
• [4] Amoxicillin FDA Label
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• [6] The mechanism of action of chlorhexidine. FEMS Microbiol Lett. 1992 Dec 15;79(1-3):211-5.
• [7] Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition. Environ Health Perspect. 2021 Apr;129(4):47008. doi: 10.1289/EHP6993. Epub 2021 Apr 12.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
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• [13] Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Mol Nutr Food Res. 2013 Mar;57(3):523-35.
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• [15] ACI-1 beta-lactamase is widespread across human gut microbiomes in Negativicutes due to transposons harboured by tailed prophages. Environ Microbiol. 2018 Jun;20(6):2288-2300.
• [16] Beta-lactamase production and susceptibilities to amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-Bacteroides fragilis Bacteroides isolates and 129 fusobacteria from 28 U.S. centers. Antimicrob Agents Chemother. 1990 Aug;34(8):1546-50.
• [17] Detection and characterization of beta-lactamase genes in subgingival bacteria from patients with refractory periodontitis. FEMS Microbiol Lett. 2005 Jan 15;242(2):319-24.
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• [19] A novel quorum-quenching N-acylhomoserine lactone acylase from Acidovorax sp. strain MR-S7 mediates antibiotic resistance. Appl Environ Microbiol. 2017 Jun 16;83(13). pii: e00080-17.
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• [21] Presence of the cfxA gene in Bacteroides distasonis. Res Microbiol. 2003 Jun;154(5):369-74.
• [22] Prevotella strains and lactamic resistance gene distribution in different oral environments of children with pulp necrosis. Int Endod J. 2018 Nov;51(11):1196-1204.
• [23] Interspecies dissemination of a mobilizable plasmid harboring blaIMP-19 and the possibility of horizontal gene transfer in a single patient. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5412-9.
• [24] IncU plasmid harbouring bla CTX-M-8 in multidrug-resistant Shigella sonnei in Brazil. J Glob Antimicrob Resist. 2018 Sep;14:99-100.
• [25] High prevalence of beta-lactam and macrolide resistance genes in human oral Capnocytophaga species. J Antimicrob Chemother. 2014 Feb;69(2):381-4.
• [26] Yersinia enterocolitica and Photorhabdus asymbiotica beta-lactamases BlaA are exported by the twin-arginine translocation pathway. Int J Med Microbiol. 2013 Jan;303(1):16-24.
• [27] Genomic characterization of an extensively-drug resistance Salmonella enterica serotype Indiana strain harboring bla NDM-1 gene isolated from a chicken carcass in China. Microbiol Res. 2017 Nov;204:48-54.
• [28] High prevalence of cfxA beta-lactamase in aminopenicillin-resistant Prevotella strains isolated from periodontal pockets. Oral Microbiol Immunol. 2002 Apr;17(2):85-8.
• [29] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
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